The overarching goal of this project is to define a mechanistic basis for the process of animal regeneration. This project takes advantage of methodological advances and findings obtained during the last funding period to: 1) define a high temporal resolution, genome-wide, expression profile of regeneration; 2) interrogate the functions of known embryonic signaling pathways in the adult contexts of tissue regeneration and homeostasis, and to carry out a formal comparison of how the mechanisms of regeneration compare to embryogenesis; 3) uncover genes involved in the regeneration of adult organs after amputation; and 4) Initiate comparative studies of regeneration to test the universality of our findings. All three lines of investigation synergize with each other and their integration should provide us with a high-resolution set of molecular processes regulating regeneration and regenerative capacities. Thus far, this approach has led us to uncover novel animal cell biology and functions in adult contexts of known genes, and to define functions for the many conserved animal genes for which functions are still unknown. Given the high degree of evolutionary conservation that exits between planarians and vertebrates, the characterization of gene functions in planarians will advance efforts to study human stem-cell function, regeneration and wound healing, effectively advancing these frontiers of human health. RELEVANCE (See instructions): The overarching goal of this project is to define a mechanistic basis for the process of animal regeneration. Given the high degree of evolutionary conservation that exits between planarians and vertebrates, the characterization of gene functions in planarians will advance efforts to study human stem-cell function, regeneration and wound healing, effectively advancing these frontiers of human health.